Mammalian lung development: Interactions in primordium formation and bronchial morphogenesis

Abstract

The manner in which mouse lung primordia form has been analyzed by observation of trypsin‐isolated gut endoderm from nine‐day embryos. The tissue interactions involved in initial formation of lung primordia and those involved in subsequent morphogenesis of the primordia have been investigated by various organ culture procedures. Mouse lungs form in a manner different from that generally described for amniote embryos. Thus, two lung buds appear first and form the primary bronchi, whereas the trachea appears secondarily. The initial lung buds form at the 25–27 somite stage. Whole‐guts from embryos as young as the two‐somite stage form lung buds in culture. Such buds do not undergo branching morphogenesis if the guts are taken from embryos younger than the 25‐somite stage, but undergo characteristic dichotomous branching if combined with older bronchial mesoderm. If 20–25 somite‐stage endoderm is isolated and cultured in direct combination with gut, older salivary or older bronchial mesoderms, lung buds form. However, such buds only branch in combinations containing bronchial mesoderm. Our results reveal two levels of mesodermal control of lung development. Interactions between nonspecific mesoderm and gut endoderm result in lung bud formation, while those between specific bronchial mesoderm and bud endoderm are required for branching morphogenesis.